Diisopropylethylamine → HCID 86668926, compound

HRID 2281860Notes

Reaction equation

HRID 2281860 reaction equation
C(N(C(C)C)C(C)C)C.[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([F:41])=[C:15]([C@:17]23[CH2:25][O:24][C@H:23]([C:26]([F:29])([F:28])[F:27])[C@H:22]2[C:21](=[O:30])[N:20]([CH2:31][CH3:32])[C:19]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[N:18]3)[CH:16]=1.[F:42][CH:43]([F:53])[C:44]1[N:45]=[CH:46][C:47]([C:50](O)=[O:51])=[N:48][CH:49]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>C(Cl)Cl>[F:53][CH:43]([F:42])[C:44]1[N:45]=[CH:46][C:47]([C:50]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([F:41])=[C:15]([C@:17]34[CH2:25][O:24][C@H:23]([C:26]([F:29])([F:27])[F:28])[C@H:22]3[C:21](=[O:30])[N:20]([CH2:31][CH3:32])[C:19]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:39])[CH3:38])=[N:18]4)[CH:16]=2)=[O:51])=[N:48][CH:49]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 574685755-Difluoromethympyrazine-2-carboxylic acidHCID 69937498HCID 69937498, compound

Product 1

HCID 86668926HCID 86668926, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-Ethyl-N-(propan-2-yl)propan-2-amine (190 μL, 1.1 mmol) was added to a stirred mixture of tert-butyl ((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-3-ethyl-4-oxo-5-(trifluoromethyl)-3,4,4a,5,7,7a-hexahydrofuro[3,4-d]pyrimidin-2-yl)carbamate (100 mg, 0.21 mmol), 5-(difluoromethyl)pyrazine-2-carboxylic acid (57 mg, 0.33 mmol) and (1H-benzotriazol-1-yloxy)(tripyrrolidin-1-yl)phosphonium hexafluorophosphate (170 mg, 0.33 mmol) in dry DCM (1 mL) at RT under nitrogen. The reaction was stirred at this temperature for 16 h, and then partitioned between DCM and NaHCO3 (aq.). The aqueous layer was extracted with DCM (×2). The combined extracts were dried by passing through a hydrophobic frit and then evaporated. The residue was purified by column chromatography (normal phase, 10 g, Biotage SNAP cartridge KP-Sil, 12 mL per min, gradient 5% to 30% EtOAc in n-hexane) to give the title compound (118 mg, cream foam). 1H NMR (400 MHz, CDCl3-d) δ ppm 1.14 (t, J=7.07 Hz, 3H) 1.56 (s, 9H) 3.96-4.15 (m, 3H) 4.39 (d, J=9.60 Hz, 1H) 4.50 (dd, J=9.73, 2.91 Hz, 1H) 4.53-4.62 (m, 1H) 6.81 (t, J=54.60 Hz, 1H) 7.22 (dd, J=10.74, 8.97 Hz, 1H) 7.76 (dd, J=6.69, 2.65 Hz, 1H) 7.79-7.84 (m, 1H) 8.93 (s, 1H) 9.52 (s, 1H) 9.65 (s, 1H) 10.64 (s, 1H).

Workup

  1. custompartitioned between DCM and NaHCO3 (aq.)
  2. extractionThe aqueous layer was extracted with DCM (×2)
  3. customThe combined extracts were dried
  4. customevaporated
  5. customThe residue was purified by column chromatography (normal phase, 10 g, Biotage SNAP cartridge KP-Sil, 12 mL per min, gradient 5% to 30% EtOAc in n-hexane)

Sources & evidence

ORD record
ord-c147554b9f534f4c9cf6b097c2da0629
Source dataset
uspto-grants-2015_09
Patent number
US09139594B2

Reaction notes

Loading…